Lee E B, Kim J Y, Zhao J, Park M H, Song Y W
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Tissue Antigens. 2007 Feb;69(2):128-32. doi: 10.1111/j.1399-0039.2006.00736.x.
Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of Behcet's disease (BD). To investigate the association of the genetic polymorphism of IL-8 and BD, we genotyped IL-8 -845 T/C, -738 T/A, -353 A/T, -251 A/T, +293 G/T, +678 T/C and receptors CXCR-1 +2607 G/C and CXCR-2 +785 C/T polymorphisms in 119 Korean patients with BD and 119 age- and sex-matched healthy blood donors. Then, single nucleotide polymorphisms (SNPs) and haplotypes were analyzed between patients and controls. There were no SNPs associated with BD. However, the frequency of haplotype TAT inferred from SNPs, IL-8 -353 A/T, -251 A/T and +678 T/C, was significantly higher in patients with BD than controls (5.9 vs 0.0%, P = 0.0001), as was haplotype ATC (6.7 vs 0.0%, P < 0.0001). The haplotype difference was still valid in human leukocyte antigen-B51-negative subjects. In conclusion, we found a significant difference in the distribution of IL-8 gene haplotypes between patients with BD and healthy controls. These results suggest that the genetic polymorphisms of proinflammatory chemokine IL-8 can contribute to the pathogenesis of BD.
白细胞介素-8(IL-8)是一种招募和激活炎症细胞的CXC趋化因子,在白塞病(BD)的发病机制中起关键作用。为了研究IL-8基因多态性与BD的关联,我们对119例韩国BD患者和119例年龄及性别匹配的健康献血者进行了IL-8 -845 T/C、-738 T/A、-353 A/T、-251 A/T、+293 G/T、+678 T/C多态性以及受体CXCR-1 +2607 G/C和CXCR-2 +785 C/T多态性的基因分型。然后,分析了患者和对照组之间的单核苷酸多态性(SNP)和单倍型。未发现与BD相关的SNP。然而,由SNP(IL-8 -353 A/T、-251 A/T和+678 T/C)推断出的单倍型TAT在BD患者中的频率显著高于对照组(5.9%对0.0%,P = 0.0001),单倍型ATC也是如此(6.7%对0.0%,P < 0.0001)。在人类白细胞抗原-B51阴性受试者中,单倍型差异仍然有效。总之,我们发现BD患者与健康对照组之间IL-8基因单倍型的分布存在显著差异。这些结果表明,促炎趋化因子IL-8的基因多态性可能有助于BD的发病机制。